Saccharide hydrazones

The saccharide derivatives best suited for cyclization to pyrazolines and pyrazoles are the hydrazones and osazones, which possess the two adjacent nitrogen atoms required. 

So far so good. But how can the fourth double bond be created There is a possibility of dehydrogenation of -CH-NH- group by hydrazine, similar to that of dehydrogenation of -CH-OH bond in saccharides by phenylhydrazine, which is hydrogenolyzed to ammonia and aniline. Here the molecule of cyclobutanetetronetetrakis(hydrazone), Z, is obtained, and hydrazine is split to ammonia [52]. 

The chemistry of carba sugars is quite similar to that of cyclitols both groups lack the latent carbonyl groups of their saccharide counterparts, and therefore fail to exhibit many of the characteristic properties of monosaccharides. Thus carba sugars and cyclitols do not form hydrazones or osazones, nor do they mutarotate, or reduce heavy-metal salts in base, in contrast to their oxidation products, the inososes. 

The structure of inosose mono(phenylhydrazones) is quite similar to that of acyclic saccharide hydrazones neither possess chelated rings and both exist in the Schiff-base form. Cyclization to hydrazino forms, a common process among many saccharide hydrazones, has not been observed in inosose hydrazones, probably because the resulting bicyclic compounds would be unduly strained or rigid. 

The infrared spectra of phenylosazones have also been studied in detail, and have been suggested as a means of identification of the different saccharide osazones. Saccharide osazones show the characteristic hydroxyl bands at 3 n, the C=N band of the hydrazone residues at 6.3 n, and three bands attributed to the phenyl ring. In the case of acetylated osazones, the 0-acetyl band appears at 1735 cm. and JV-acetylated derivatives show the A-acetyl band at " about 1640 cm.. These characteristics have greatly simplified the differentiation of 0-acetyl from iV-acetyl groups in acetylated osazones. Also, for benzoylated osazones, the differentiation offers no difficulty the 0-benzoyl band appears at 1725 cm. and the A-benzoyl band at 1685 cm.. ... 

The hydrazine derivatives of saccharide are here discussed in sections on saccharide azines, which are formed when one hydrazine molecule reacts with two saccharide molecules saccharide hydrazones and glycosylhy-drazines, which are the tautomeric acyclic and cyclic products formed when one hydrazine molecule reacts with one sugar residue saccharide osazones and poly(hydrazones), which are formed when two or more hydrazine molecules are linked to a saccharide residue and, finaly, hydrazones of carba-sugars and related compounds. 

Saccharide hydrazones are prepared by treating aldoses, ketoses, al-dosuloses, or reducing disaccharides with unsubstituted hydrazine 81 82 with monosubstituted hydrazines having alkyl,81 acyl,30-83 84 aroyl85 sul-fonyl,36,39-40,86 8 aryl,89-93 or disubstituted tyiV-dialkyl-,81 AUY-diaryl-,94 or... 

Although saccharide hydrazones exist in solution as equilibrium mixtures of several forms, the crystalline hydrazones isolated from solution are usually composed of only one form, which is often the most stable one in the medium. It is to be expected that substituted hydrazines would afford two types of products, one formed by nucleophilic attack of N-l and one by N-2. This expectation was confirmed when phenylazostyrene (18) was treated with phenylhydrazine (19) at low temperature and the rate-controlled N-l adduct (21) was isolated from the reaction mixture and converted into benzil bis(phenylhydrazone) (20) by heating. It may be assumed that the reaction proceeds by the conversion of the rate-controlled N-l adduct to the equilibrium-controlled N-2 adduct (not depicted), followed by an oxidation step (Scheme 5).115,116... 

The hydrazones of sugars are capable of existing in various cyclic forms, whose presence is apparent from their nuclear magnetic resonance (NMR) spectra and from the complex mutarotation curves they exhibit110,111117118 (which seldom follow first-order kinetics). The principal structures encountered in saccharide hydrazones are the acyclic, Schiff base-type true hydrazones and the cyclic hydrazino forms, namely glycopyranosyl- and gly-cofuranosylhydrazines. For example, three isomeric forms of D-glucose phenylhydrazone have been isolated.119 The Schiff base derivatives can be... 

Saccharide hydrazones can exist in several tautomeric forms, which include the phenylazo and enehydrazine forms. 

Because of the similarity between the C=0 group of acyclic monosaccharides and the C=N group of their hydrazones, the latter exhibit many of the reactions of their parent saccharides for example, they are susceptible... 

Acetylation of saccharide hydrazones (65) with acetic anhydride in pyridine affords per-O-acetylatcd derivatives (such as 66) with acyclic hydrazones and A-acetyl-O-acetyl derivatives with the cyclic ones. 5 "4 t 4,i63 jn [1C as, casC [lc [sjpi group attached to the aryl moiety is not acetylated, but the more basic NH group attached to the sugar moiety is acetylated. The 0-acetyl groups are split off by base more readily than the iV-acctyl groups.218 and methods for selective saponification have been devised. With acetyl chloride in A/, A-tli methyl aniline, the NH group attached to the aryl residue becomes acylated and acyclic hexose hydrazones give A-acetyl-penta-O-acctyl derivatives (64) 165 similarly, benzoylation with benzoyl chloride in pyridine affords W-benzoyl-0-bcnzoyl deri vatives (Scheme 15)219... 

Formation of Pyrazoles from Bis(hydrazones).—Mesoxaldehyde bis(phenylhydrazone) (193), obtained by periodate oxidation of saccharide osazones (192) is readily cyclized in the presence of acids to give l-phenyl-4-phenylazo-pyrazole (195).162 365 Hexulose phenylosazones (192) are also disproportionaled in the presence of acidic salts of carbonyl reagents, such as hydroxylamine hydrochloride, to give l-phenyl-4-phenylazo-pyrazolin-5-one (196). The reaction probably proceeds via mesoxalic acid 1,2-bis(phenylhydrazone) (194).365 The hydroxalkyl derivatives of 196 are produced from dehydroascorbic acid bis(phenylhydrazone) by treatment with base to open the lactone ring and permit the conversion of 197 to 199.351,366 Another type of pyrazole that is formed by dehydrating osazones with acetic anhydride is discussed later under anhydroosazones (see Schemes 45,53). 

Triose tris(hydrazones) may also be obtained from periodate-oxidized saccharide bis(hydrazones)313 365 (239) by treating the resulting mesoxalde-hyde bis(benzoylhydrazone) (240) with benzoylhydrazine. Mesoxalalde-hyde tris(benzoylhydrazone) (241) was found to react with iodine in a manner similar to that of hexosulose bis(benzoylhydrazones) to give a triazole derivative408 242 (Scheme 58). 

Iii this chapter on the hydrazine derivatives of sugars and related compounds, an attempt has been made to offer more than a review of what has already been achieved by focusing on reactions that have not yet been tried on carbohydrate substrates (examples of these are given in Sections III.3 and IV.4). In summary, a serious effort has been made to point to novel approaches for the synthesis of, and new applications for, the reactions of saccharide hydrazones and their carbocyclic analogs. 

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